Delivery of replication-competent retrovirus expressing Escherichia coli purine nucleoside phosphorylase increases the metabolism of the prodrug, fludarabine phosphate and suppresses the growth of bladder tumor xenografts

Eiji Kikuchi, S. Menendez, C. Ozu, M. Ohori, C. Cordon-Cardo, C. R. Logg, N. Kasahara, B. H. Bochner

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

We have developed unique replication-competent retroviral (RCR) vectors based on murine leukemia virus that provide improved efficiency of viral delivery, allow for long-term transgene expression and demonstrate an intrinsic selectivity for transduction of rapidly dividing tumor cells. The purpose of this study was to evaluate the in vivo transduction efficiency and the therapeutic efficacy of the RCR vector mediated delivery of Escherichia coli purine nucleoside phosphorylase (PNP) in combination with fludarabine phosphate for bladder cancer. We constructed vectors containing green fluorescent protein (GFP) gene (ACE)-GFP) or PNP gene (ACE-PNP). KU-19-19 bladder tumors exhibited 28.3±16.1, 46.6±5.8 and 93.7±7.8% of GFP expression on 14, 18 and 26 days after intratumoral injection of ACE-GFP, respectively. GFP expression could not be observed in normal tissues surrounding the injected tumors. No detectable polymerase chain reaction products of GFP gene could be observed in any distant organs. Intratumoral injection of ACE-PNP, followed by systemically administered fludarabine phosphate, significantly inhibited the growth of pre-established KU-19-19 tumors. Our results indicate that RCR vectors are a potentially efficient gene delivery method and that the RCR vector mediated PNP gene transfer and fludarabine phosphate treatment might be a novel and potentially therapeutic modality for bladder cancer.

Original languageEnglish
Pages (from-to)279-286
Number of pages8
JournalCancer Gene Therapy
Volume14
Issue number3
DOIs
Publication statusPublished - 2007 Mar
Externally publishedYes

Fingerprint

fludarabine phosphate
Purine-Nucleoside Phosphorylase
Prodrugs
Retroviridae
Green Fluorescent Proteins
Heterografts
Urinary Bladder Neoplasms
Escherichia coli
Growth
Genes
Murine Leukemia Viruses
Neoplasms
Injections
Transgenes
Therapeutics

Keywords

  • Fludarabine phosphate
  • Purine nucleoside phosphorylase
  • Retroviral vector
  • Suicide gene

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Delivery of replication-competent retrovirus expressing Escherichia coli purine nucleoside phosphorylase increases the metabolism of the prodrug, fludarabine phosphate and suppresses the growth of bladder tumor xenografts. / Kikuchi, Eiji; Menendez, S.; Ozu, C.; Ohori, M.; Cordon-Cardo, C.; Logg, C. R.; Kasahara, N.; Bochner, B. H.

In: Cancer Gene Therapy, Vol. 14, No. 3, 03.2007, p. 279-286.

Research output: Contribution to journalArticle

Kikuchi, Eiji ; Menendez, S. ; Ozu, C. ; Ohori, M. ; Cordon-Cardo, C. ; Logg, C. R. ; Kasahara, N. ; Bochner, B. H. / Delivery of replication-competent retrovirus expressing Escherichia coli purine nucleoside phosphorylase increases the metabolism of the prodrug, fludarabine phosphate and suppresses the growth of bladder tumor xenografts. In: Cancer Gene Therapy. 2007 ; Vol. 14, No. 3. pp. 279-286.
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